Publications by authors named "Xiaolong Liu"

458 Publications

Semi-Automatic Planning and Three-dimensional Electrospinning of Patient-Specific Grafts for Fontan Surgery.

IEEE Trans Biomed Eng 2021 Jun 22;PP. Epub 2021 Jun 22.

This paper proposes a semi-automatic Fontan surgery planning method for designing and manufacturing hemodynamically optimized patient-specific grafts. Fontan surgery is a palliative procedure for patients with a single ventricle heart defect by creating a new path using a vascular graft for the deoxygenated blood to be directed to the lungs, bypassing the heart. However, designing patient-specific grafts with optimized hemodynamic performance is a complex task due to the variety of patient-specific anatomies, confined surgical planning space, and the requirement of simultaneously considering multiple design criteria for vascular graft optimization. To address these challenges, we used parameterized Fontan pathways to explore patient-specific vascular graft design spaces and search for optimal solutions by formulating a nonlinear constrained optimization problem, which minimizes indexed power loss (iPL) of the Fontan model by constraining hepatic flow distribution (HFD), percentage of abnormal wall shear stress (%WSS) and geometric interference between Fontan pathways and the heart models (InDep) within clinically acceptable thresholds. Gaussian process regression was employed to build surrogate models of the hemodynamic parameters as well as InDep and Nv (conduit model smoothness indicator) for optimization by pattern search. We tested the proposed method on two patient-specific models (n=2). The results showed the automatically optimized (AutoOpt) Fontan models hemodynamically outperformed or at least are comparable to manually optimized Fontan models with significantly reduced surgical planning time (15 hours versus over 2 weeks). We also demonstrated feasibility of manufacturing the AutoOpt Fontan conduits by using electrospun nanofibers.
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http://dx.doi.org/10.1109/TBME.2021.3091113DOI Listing
June 2021

Redirecting natural killer cells to potentiate adoptive immunotherapy in solid tumors through stabilized Y-type bispecific aptamer.

Nanoscale 2021 Jun 22. Epub 2021 Jun 22.

The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, P. R. China and The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, P. R. China.

Modulating interactions between immune effector cells and tumor cells in vivo using a bispecific aptamer (Ap) is a promising strategy for cancer immunotherapy. However, it remains a technical challenge owing to the complex and dynamic internal environment accompanied by severe degradation. Herein, by using a Y-shaped DNA scaffold, a bispecific and stabilized Y-type Ap is designed to redirect natural killer (NK) cells to enhance adoptive immunotherapy of hepatocellular carcinoma (HCC) solid tumors. Y-type Ap is constituted by the HCC-specific Ap TLS11a linked with the CD16-specific Ap through a Y-shaped DNA scaffold. Owing to the rigid structure, Y-type Ap shows high stability in 10% serum for over 72 h and resistance to denaturation by 8 M urea. Additionally, the Y-type Ap exhibits more potent avidity to bind with NK cells and tumor cells both in vitro and in vivo, resulting in higher cytokine secretion and excellent antitumor efficiency. Collectively, this study offers a translational platform for constructing stable bispecific Ap, offering considerable potential to enhance adoptive immunotherapy of solid tumors.
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http://dx.doi.org/10.1039/d1nr00836fDOI Listing
June 2021

RBC Membrane Camouflaged Semiconducting Polymer Nanoparticles for Near-Infrared Photoacoustic Imaging and Photothermal Therapy.

Nanomicro Lett 2020 Apr 20;12(1):94. Epub 2020 Apr 20.

School of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, 350002, People's Republic of China.

Semiconducting conjugated polymer nanoparticles (SPNs) represent an emerging class of phototheranostic materials with great promise for cancer treatment. In this report, low-bandgap electron donor-acceptor (D-A)-conjugated SPNs with surface cloaked by red blood cell membrane (RBCM) are developed for highly effective photoacoustic imaging and photothermal therapy. The resulting RBCM-coated SPN ([email protected]) displays remarkable near-infrared light absorption and good photostability, as well as high photothermal conversion efficiency for photoacoustic imaging and photothermal therapy. Particularly, due to the small size (< 5 nm), [email protected] has the advantages of deep tumor penetration and rapid clearance from the body with no appreciable toxicity. The RBCM endows the SPNs with prolonged systematic circulation time, less reticuloendothelial system uptake and reduced immune-recognition, hence improving tumor accumulation after intravenous injection, which provides strong photoacoustic signals and exerts excellent photothermal therapeutic effects. Thus, this work provides a valuable paradigm for safe and highly efficient tumor photoacoustic imaging and photothermal therapy for further clinical translation.
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http://dx.doi.org/10.1007/s40820-020-00429-xDOI Listing
April 2020

Tumor Microenvironment Cascade-Responsive Nanodrug with Self-Targeting Activation and ROS Regeneration for Synergistic Oxidation-Chemotherapy.

Nanomicro Lett 2020 Sep 14;12(1):182. Epub 2020 Sep 14.

CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, 350002, People's Republic of China.

Carrier-free nanodrug with exceptionally high drug payload has attracted increasing attentions. Herein, we construct a pH/ROS cascade-responsive nanodrug which could achieve tumor acidity-triggered targeting activation followed by circularly amplified ROS-triggered drug release via positive-feedback loop. The di-selenide-bridged prodrug synthesized from vitamin E succinate and methotrexate (MTX) self-assembles into nanoparticles (VSeM); decorating acidity-cleavable PEG onto VSeM surface temporarily shields the targeting ability of MTX to evade immune clearance and consequently elongate circulation time. Upon reaching tumor sites, acidity-triggered detachment of PEG results in targeting recovery to enhance tumor cell uptake. Afterward, the VSeM could be dissociated in response to intracellular ROS to trigger VES/MTX release; then the released VES could produce extra ROS to accelerate the collapse of VSeM. Finally, the excessive ROS produced from VES could synergize with the released MTX to efficiently suppress tumor growth via orchestrated oxidation-chemotherapy. Our study provides a novel strategy to engineer cascade-responsive nanodrug for synergistic cancer treatment.
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http://dx.doi.org/10.1007/s40820-020-00492-4DOI Listing
September 2020

A remotely controlled NIR-II photothermal-sensitive transgene system for hepatocellular carcinoma synergistic therapy.

J Mater Chem B 2021 Jun 14. Epub 2021 Jun 14.

The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China. and Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, People's Republic of China and Mengchao Med-X Center, Fuzhou University, Fuzhou 350116, People's Republic of China and Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou 350014, P. R. China.

Photothermal therapy (PTT) exhibits an excellent therapeutic effect in cancer treatment, but some cancers are still facing rapid recurrence due to the presence of heat-resistant cells, which express heat shock proteins (HSP) to defend against hyperthermia. Inspired by optogenetics, we firstly designed a caged TNF-related apoptosis-inducing ligand (TRAIL) expressing plasmid under HSP70 protomer (HSP70-TRAIL) as the thermal-activated gene therapy agent to induce the apoptosis of heat resistant cells. Then, the caged HSP70-TRAIL was decorated on the surface of the photothermal agent (semiconducting nanoparticles, SPNs) through electrostatic adsorption to obtain [email protected] (SPNHT). Under 1064 nm near-infrared second region (NIR-II) laser irradiation, the SPNHT acted as an emerging photothermal agent for PTT. Importantly, the caged HSP70-TRAIL could be further activated by PTT to express TRAIL on demand to concurrently kill survival cells for overcoming the problem of tumor recurrence after PTT. Both in vitro and in vivo studies demonstrated that the SPNHT nano-system with the ability of NIR-II photothermal-triggered TRAIL in situ expression possessed an admirable synergistic anti-cancer efficacy for HCC. This work offers new tactics for effective treatment of cancer, which showed a great significance for reducing the rate of cancer recurrence after PTT treatment.
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http://dx.doi.org/10.1039/d1tb00493jDOI Listing
June 2021

YB1 regulates miR-205/200b-ZEB1 axis by inhibiting microRNA maturation in hepatocellular carcinoma.

Cancer Commun (Lond) 2021 Jun 10. Epub 2021 Jun 10.

CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning, 116023, P. R. China.

Background: Y-box binding protein 1 (YB1 or YBX1) plays a critical role in tumorigenesis and cancer progression. However, whether YB1 affects malignant transformation by modulating non-coding RNAs remains largely unknown. This study aimed to investigate the relationship between YB1 and microRNAs and reveal the underlying mechanism by which YB1 impacts on tumor malignancy via miRNAs-mediated regulatory network.

Methods: The biological functions of YB1 in hepatocellular carcinoma (HCC) cells were investigated by cell proliferation, wound healing, and transwell invasion assays. The miRNAs dysregulated by YB1 were screened by microarray analysis in HCC cell lines. The regulation of YB1 on miR-205 and miR-200b was determined by quantitative real-time PCR, dual-luciferase reporter assay, RNA immunoprecipitation, and pull-down assay. The relationships of YB1, DGCR8, Dicer, TUT4, and TUT1 were identified by pull-down and coimmunoprecipitation experiments. The cellular co-localization of YB1, DGCR8, and Dicer were detected by immunofluorescent staining. The in vivo effect of YB1 on tumor metastasis was determined by injecting MHCC97H cells transduced with YB1 shRNA or shControl via the tail vein in nude BALB/c mice. The expression levels of epithelial to mesenchymal transition markers were detected by immunoblotting and immunohistochemistry assays.

Results: YB1 promoted HCC cell migration and tumor metastasis by regulating miR-205/200b-ZEB1 axis partially in a Snail-independent manner. YB1 suppressed miR-205 and miR-200b maturation by interacting with the microprocessors DGCR8 and Dicer as well as TUT4 and TUT1 via the conserved cold shock domain. Subsequently, the downregulation of miR-205 and miR-200b enhanced ZEB1 expression, thus leading to increased cell migration and invasion. Furthermore, statistical analyses on gene expression data from HCC and normal liver tissues showed that YB1 expression was positively associated with ZEB1 expression and remarkably correlated with clinical prognosis.

Conclusion: This study reveals a previously undescribed mechanism by which YB1 promotes cancer progression by regulating the miR-205/200b-ZEB1 axis in HCC cells. Furthermore, these results highlight that YB1 may play biological functions via miRNAs-mediated gene regulation, and it can serve as a potential therapeutic target in human cancers.
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http://dx.doi.org/10.1002/cac2.12164DOI Listing
June 2021

AQP3-mediated H O uptake inhibits LUAD autophagy by inactivating PTEN.

Cancer Sci 2021 Jun 6. Epub 2021 Jun 6.

Department of Thoracic Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, 110042, China.

It is widely accepted that redox reprogramming participates in malignant transformation of lung adenocarcinoma (LUAD). However, the source of excessive reactive oxygen species (ROS) and the downstream signaling regulatory mechanism are complicated and unintelligible. In current study, we newly identified the aquaporin 3 (AQP3) as a LUAD oncogenic factor with capacity to transport exogenous hydrogen peroxide (H O ) and increase intracellular ROS levels. Subsequently, we demonstrated that AQP3 was necessary for the facilitated diffusion of exogenous H O in LUAD cells and that the AQP3-dependent transport of H O accelerated cell growth and inhibited rapamycin-induced autophagy. Mechanistically, AQP3-mediated H O uptake increased intracellular ROS levels to inactivate PTEN and activate the AKT/mTOR pathway subsequently inhibit autophagy and 1promote proliferation in LUAD cells. Finally, we suggested that AQP3 depletion retarded subcutaneous tumorigenesis in vivo and simultaneously decreased ROS levels and promoted autophagy. These findings underscore the importance of AQP3-induced oxidative stress in malignant transformation and suggest a therapeutic target for LUAD.
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http://dx.doi.org/10.1111/cas.15008DOI Listing
June 2021

Imparting Ion Selectivity to Covalent Organic Framework Membranes Using Assembly for Blue Energy Harvesting.

J Am Chem Soc 2021 May 24. Epub 2021 May 24.

Zhejiang Provincial Key Laboratory of Advanced Chemical Engineering Manufacture Technology, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.

It has long been a challenge to fabricate angstrom-sized functional pores for mimicking the function of biological channels to afford selective transmembrane transport. In this study, we describe a facile strategy to incorporate ionic elements into angstrom-sized channels using encapsulation of charged dye molecules during the interface polymerization of a three-dimensional covalent organic framework (3D COF). We demonstrate that this approach is tailorable as it enables control over both the type and content of the guest and thus allows manipulation of the membrane function. The resulting membranes exhibit excellent permselectivity and low membrane resistance, thereby indicating the potential for harvesting salinity gradient (blue) energy. As a proof-of-concept study, the reverse electrodialysis device coupled with positive and negative dye encapsulated COF membranes afforded a power density of up to 51.4 W m by mixing the simulated seawater and river water, which far exceeds the commercialization benchmark (5 W m). We envision that this strategy will pave the way for constructing new multifunctional biomimetic systems.
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http://dx.doi.org/10.1021/jacs.1c02090DOI Listing
May 2021

O oxidation combined with semi-dry method for simultaneous desulfurization and denitrification of sintering/pelletizing flue gas.

J Environ Sci (China) 2021 Jun 23;104:253-263. Epub 2020 Dec 23.

CAS Key Laboratory of Green Process and Engineering, Institute of Process Engineering, Innovation Academy for Green Manufacture, Chinese Academy of Sciences, Beijing 100190, China.

With the vigorous development of China's iron and steel industry and the introduction of ultra-low emission policies, the emission of pollutants such as SO and NO has received unprecedented attention. Considering the increase of the proportion of semi-dry desulfurization technology in the desulfurization process, several semi-dry desulphurization technologies such as flue gas circulating fluidized bed (CFB), dense flow absorber (DFA) and spray drying absorption (SDA) are briefly summarized. Moreover, a method for simultaneous treatment of SO and NO in sintering/pelletizing flue gas by O oxidation combined with semi-dry method is introduced. Meantime, the effects of key parameters such as O/NO molar ratio, CaSO, SO, reaction temperature, Ca/(S+2N) molar ratio, droplet size and approach to adiabatic saturation temperature (AAST) on denitrification and desulfurization are analyzed. Furthermore, the reaction mechanism of denitrification and desulfurization is further elucidated. Finally, the advantages and development prospects of the new technology are proposed.
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http://dx.doi.org/10.1016/j.jes.2020.11.021DOI Listing
June 2021

A highly stable multifunctional aptamer for enhancing antitumor immunity against hepatocellular carcinoma by blocking dual immune checkpoints.

Biomater Sci 2021 Jun;9(11):4159-4168

The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, P. R. China. and Fujian Institute of Research on The Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, P. R. China.

T-lymphocytes play a potent role in cancer immunotherapy; while, limited tumor infiltrating lymphocytes (TILs) combined with severe immunosuppression always significantly hinder their antitumor immune responses, especially in solid tumors such as hepatocellular carcinoma (HCC). Here, we prepared a highly stable multifunctional aptamer for strengthening antitumor immunity against HCC solid tumors through a dual immune checkpoint blockade of CTLA-4 and PD-L1. The engineered multifunctional aptamer (termed P1/C4-bi-apt) can block both CTLA-4/B7 and PD-1/PD-L1 signaling pathways and thus enhance the antitumor immune responses. Furthermore, it can direct CTLA-4-positive T cells to infiltrate into tumors to further enhance the antitumor efficacy compared to a single blockage of CTLA-4 or PD-L1. As a result, the multifunctional aptamer can significantly inhibit tumor growth and thus improve the long-term survival of HCC-bearing mice. The designed multifunctional aptamer is simple, stable and easy to prepare, and it can significantly strengthen the functionality of T cells, holding great potential for HCC immunotherapy.
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http://dx.doi.org/10.1039/d0bm02210aDOI Listing
June 2021

Development of Prognostic Evaluation Model to Predict the Overall Survival and Early Recurrence of Hepatocellular Carcinoma.

J Hepatocell Carcinoma 2021 29;8:301-312. Epub 2021 Apr 29.

The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, 350025, People's Republic of China.

Background: The aberrant expressions of lncRNAs have been frequently demonstrated to be closely associated with the prognosis of patients in many cancer types including hepatocellular carcinoma (HCC). Integration of these lncRNAs might provide accurate evaluation of HCC. Therefore, this study aims to develop a novel prognostic evaluation model based on the expression of lncRNAs to predict the survival of HCC patients, postoperatively.

Patients And Methods: RNA sequencing (RNA-seq) analysis was performed for 61 HCC patients (training cohort) to screen prognosis-associated lncRNAs with univariate Cox regression and Log rank test analyses. Multivariate Cox regression analysis was then applied to establish the final model, which was further verified in a validation cohort (n=191). Moreover, performance of the mode was assessed with time-dependent receiver operating characteristic curve (tdROC), Harrell's c-index, and Gönen & Heller's K.

Results: After a serial statistical computation, a novel risk scoring model consisting of four lncRNAs and TNM staging was established, which could successfully divide the HCC patients into low-risk and high-risk groups with significantly different OS and RFS in both training and validation cohorts. tdROC analysis showed that this model achieved a high performance in predicting OS and 2-year RFS in both cohorts. Gene Set Enrichment Analysis revealed that HCC tumor tissues with high-risk score have stronger capacities in immune escape and resistance to treatment.

Conclusion: We successfully established a novel prognostic evaluation model, which exhibited reliable capacity in predicting the OS and early recurrence of HCC patients with relatively higher accuracy.
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http://dx.doi.org/10.2147/JHC.S303330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092946PMC
April 2021

Chromatin assembly factor 1B critically controls the early development but not function acquisition of invariant natural killer T cells in mice.

Eur J Immunol 2021 May 5. Epub 2021 May 5.

State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, P. R. China.

CD4 CD8 double-positive thymocytes give rise to both conventional TCRαβ T cells and invariant natural killer T cells (iNKT cells), but these two kinds of cells display different characteristics. The molecular mechanism underlying iNKT cell lineage development and function acquisition remain to be elucidated. We show that the loss of chromatin assembly factor 1B (CHAF1b) maintains the normal development of conventional TCRαβ T cells but severely impairs early development of iNKT cells. This dysregulation is accompanied by the impairment in chromatin activation and gene transcription at Vα14-Jα18 locus. Notably, ectopic expression of a Vα14-Jα18 TCR rescues Chaf1b-deficient iNKT cell developmental defects. Moreover, cytokine secretion and antitumor activity are substantially maintained in Vα14-Jα18 TCR transgene-rescued Chaf1b-deficient iNKT cells. Our study identifies CHAF1b as a critical factor that controls the early development but not function acquisition of iNKT cells via lineage- and stage-specific regulation.
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http://dx.doi.org/10.1002/eji.202049074DOI Listing
May 2021

Self-Assembled Borophene/Graphene Nanoribbon Mixed-Dimensional Heterostructures.

Nano Lett 2021 May 30;21(9):4029-4035. Epub 2021 Apr 30.

Department of Materials Science and Engineering, Northwestern University, Evanston, Illinois 60208, United States.

Atomically thin metal-semiconductor heterojunctions are highly desirable for nanoelectronic applications. However, coherent lateral stitching of distinct two-dimensional (2D) materials has traditionally required interfacial lattice matching and compatible growth conditions, which remains challenging for most systems. On the other hand, these constraints are relaxed in 2D/1D mixed-dimensional lateral heterostructures due to the increased structural degree of freedom. Here, we report the self-assembly of mixed-dimensional lateral heterostructures consisting of 2D metallic borophene and 1D semiconducting armchair-oriented graphene nanoribbons (aGNRs). With the sequential ultrahigh vacuum deposition of boron and 4,4″-dibromo--terphenyl as precursors on Ag(111) substrates, an on-surface polymerization process is systematically studied and refined including the transition from monomers to organometallic intermediates and finally demetallization that results in borophene/aGNR lateral heterostructures. High-resolution scanning tunneling microscopy and spectroscopy resolve the structurally and electronically abrupt interfaces in borophene/aGNR heterojunctions, thus providing insight that will inform ongoing efforts in pursuit of atomically precise nanoelectronics.
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http://dx.doi.org/10.1021/acs.nanolett.1c00909DOI Listing
May 2021

Growing Human Hepatocellular Tumors Undergo a Global Metabolic Reprogramming.

Cancers (Basel) 2021 Apr 20;13(8). Epub 2021 Apr 20.

Gottfried Schatz Research Center, Molecular Biology and Biochemistry, Medical University of Graz, Neue Stiftingtalstraße 6/6, 8010 Graz, Austria.

Hepatocellular carcinoma (HCC) is a common malignancy with poor prognosis, high morbidity and mortality concerning with lack of effective diagnosis and high postoperative recurrence. Similar with other cancers, HCC cancer cells have to alter their metabolism to adapt to the changing requirements imposed by the environment of the growing tumor. In less vascularized regions of tumor, cancer cells experience hypoxia and nutrient starvation. Here, we show that HCC undergoes a global metabolic reprogramming during tumor growth. A combined proteomics and metabolomics analysis of paired peritumoral and tumor tissues from 200 HCC patients revealed liver-specific metabolic reprogramming and metabolic alterations with increasing tumor sizes. Several proteins and metabolites associated with glycolysis, the tricarboxylic acid cycle and pyrimidine synthesis were found to be differentially regulated in serum, tumor and peritumoral tissue with increased tumor sizes. Several prognostic metabolite biomarkers involved in HCC metabolic reprogramming were identified and integrated with clinical and pathological data. We built and validated this combined model to discriminate against patients with different recurrence risks. An integrated and comprehensive metabolomic analysis of HCC is provided by our present work. Metabolomic alterations associated with the advanced stage of the disease and poor clinical outcomes, were revealed. Targeting cancer metabolism may deliver effective therapies for HCC.
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http://dx.doi.org/10.3390/cancers13081980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074141PMC
April 2021

The health risk assessment of Heavy Metals (HMs) in road dust based on Monte Carlo simulation and bio-toxicity: a case study in Zhengzhou, China.

Environ Geochem Health 2021 Apr 13. Epub 2021 Apr 13.

College of Environmental Engineering, Henan University of Technology, Lianhua Street 100, Zhengzhou, 450001, China.

Heavy metals (HMs) in road dust pose a significant threat to human health. The analysis of human health risks of HMs is an important theoretical basis for risk screening and management. The chemical forms and characteristics of HMs in road dust were analyzed. Based on the bio-toxicity of the different fractions of the HMs and Monte Carlo, three assessment models, including the health risk assessment based on bio-toxicity, the health risk assessment based on the Monte Carlo simulation, and the health risk assessment based on the Monte Carlo simulation and bio-toxicity, were established. Under the Traditional Model, the non-carcinogenic risks were only harmful to children, while the carcinogenic risks were not harmful to adults and children. Under the M-Traditional Model, the probability of non-carcinogenic risks being harmful to children's health was 83.17%. The probability that carcinogenic risks pose a threat to children's health was 28.61%. Considering the bio-toxicity of HMs in different chemical forms, non-carcinogenic risks and carcinogenic risks under the B-Traditional Model were all less than the corresponding critical values, indicating that the HMs in the road dust did no harm to both the adults and children. Based on the MB-Traditional Model, the chance of non-carcinogenic risks being harmful to children's health is 15.43%. Among different HMs, the non-carcinogenic risks of As are highest and the carcinogenic risks of Cr were the highest, so As and Cr should be listed as priority control contamination. MB-Traditional Model established in this study simultaneously considered bio-toxicity and random simulation and obtained more accurate results, which could provide a theoretical basis for risk analysis and management.
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http://dx.doi.org/10.1007/s10653-021-00922-1DOI Listing
April 2021

Acclimation to a broad range of nitrate strength on a euryhaline marine microalga Tetraselmis subcordiformis for photosynthetic nitrate removal and high-quality biomass production.

Sci Total Environ 2021 Aug 24;781:146687. Epub 2021 Mar 24.

Department of Pharmaceutical & Biological Engineering, School of Chemical Engineering, Sichuan University, Chengdu, Sichuan 610065, China. Electronic address:

Industrial wastewaters usually possess a wide range of nitrate strength. Microalgae-based nitrate-rich wastewater treatment could realize nitrate recovery along with CO sequestration for sustainable biomass production, but the low tolerance of the microalgal strains to high-strength nitrate restricted the treatment process. The present study comprehensively evaluated a euryhaline marine microalga Tetraselmis subcordiformis for photosynthetic nitrate removal and biomass production in synthetic wastewater with a broad range of nitrate strength (0.24-7.0 g NO-N/L). This alga could acclimate to high nitrate strength up to 3.5 g NO-N/L (HN) without compromising biomass production. Nitrate could be completely removed within four days when low nitrate (0.24 g NO-N/L, LN) was loaded. The maximum nitrate removal rate of 331 mg N/L/day and specific nitrate removal rate of 360 mg N/day/g cell was obtained under medium nitrate condition (1.8 g NO-N/L, MN). High-nitrate stress under 7.0 g NO-N/L (SHN) caused an increased light energy dissipation while decreased the density of photosystem II active reaction center, which partially protect the cells from photodamage and contributed to their acclimation to SHN. The algae also enhanced amino acid/fatty acid proportions essential for maintaining intracellular redox states to cope with the stress caused by LN or SHN. HN and SHN was in favor of protein accumulation and maintenance with enhanced proportion of essential amino acids, which entitled the algal biomass to be of high quality for animal feed applied in livestock graziery and aquaculture. LN facilitated productive starch and lipid accumulation with good quality for biofuels production. The nitrate removal rate and biomass productivity exceeded most of the microalgae reported in literature under similar conditions, which highlighted Tetraselmis subcordiformis as a potent strain for flexible nitrate-rich wastewater remediation coupled with fast CO bio-mitigation and high-quality biomass production for sustainable algal biorefinery.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146687DOI Listing
August 2021

ABT‑737, a Bcl‑2 family inhibitor, has a synergistic effect with apoptosis by inducing urothelial carcinoma cell necroptosis.

Mol Med Rep 2021 Jun 31;23(6). Epub 2021 Mar 31.

Department of Urology, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.

ABT‑737 is a recently reported inhibitor of members of the Bcl‑2 family of apoptosis regulators. However, to the best of our knowledge, its necroptosis‑inducing function in bladder cancer has not yet been researched. Thus, the present study aimed to investigate whether this Bcl‑2 family inhibitor can induce both apoptosis and necroptosis of urothelial carcinoma cells. The proliferation and survival of urothelial carcinoma cell lines treated with a combination of both Z‑VAD‑FMK as a pan‑caspase inhibitor and ABT‑737 were assessed in vitro. Z‑DNA binding protein 1 (ZBP1), receptor‑interacting protein (RIP)1 and RIP3 were knocked down using small interfering RNA in urothelial carcinoma cell lines. The protein expression levels of ZBP1, RIP1 and RIP3 following cell transfection were measured via western blot analysis. Cell viability was determined using an MTT assay. Cell invasion was examined using cell invasion assays. The expression levels of necroptosis‑related proteins, high mobility group box 1, ZBP1, mixed‑lineage kinase domain‑like protein (MLKL) and RIP3, were measured via western blotting. It was found that ABT‑737 inhibited the proliferation and invasion of bladder cancer cells by inducing cell necrosis. The data demonstrated that ZBP1 and RIP3 have main roles in the cell necrosis induced by ABT‑737. In addition, RIP3 and ZBP1, without interacting with RIP1, directly induced MLKL‑mediated programmed cell necrosis. Thus, understanding how urothelial carcinoma cells react to Bcl‑2 family inhibitors may accelerate the discovery of drugs to treat bladder cancer.
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http://dx.doi.org/10.3892/mmr.2021.12051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025475PMC
June 2021

Comparative investigation of early-onset gastric cancer.

Oncol Lett 2021 May 13;21(5):374. Epub 2021 Mar 13.

The Second Clinical Medical College, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, Gansu 730030, P.R. China.

Early-onset gastric cancer (EOGC) is a serious social burden. For patients with EOGC, typically considered as those aged <45 years, the underlying cause of the disease remains unclear. In addition, several misunderstandings of EOGC remain in clinical practice. Upon diagnosis, numerous patients with EOGC are already at an advanced stage (stage IV) of the disease and are unable to benefit from treatment. Moreover, several conclusions and data obtained from different EOGC studies appear to be to contradictory. The literature indicates that the incidence of EOGC is gradually rising, and that EOGC differs from traditional and familial gastric cancer in terms of clinicopathological characteristics. Patients with EOGC typically exhibit low survival rates, poor prognosis, rapid disease progression, a low degree of differentiation (signet-ring cell tumors are common) and rapid lymph node and distant metastasis, among other characteristics. The molecular genetic mechanisms of EOGC are also significantly different from those of traditional gastric cancer. An improved definition of EOCG may provide a reference for clinical diagnosis and treatment, and clear guidelines may serve as a basis for more accurate diagnosis and the development of effective treatment strategies.
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http://dx.doi.org/10.3892/ol.2021.12635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988708PMC
May 2021

Virus-like mesoporous silica-coated plasmonic Ag nanocube with strong bacteria adhesion for diabetic wound ulcer healing.

Nanomedicine 2021 Jun 24;34:102381. Epub 2021 Mar 24.

Shengli Clinical Medical College of Fujian Medical University, Fuzhou, PR China; Department of Gastrointestinal Surgery, Fujian Provincial Hospital, Fuzhou, PR China. Electronic address:

The Gram-positive bacterium Staphylococcus aureus (MRSA) and the Gram-negative bacillus Escherichia coli (E. coli) can be commonly found in diabetic foot ulcers. However, the multi-drug resistant pathogenic bacteria infection is often difficult to eradicate by the conventional antibiotics and easy to spread which can lead to complications such as gangrene or sepsis. In this work, in order to pull through the low cell wall adhesion capability of typical antibacterial Ag nanoparticles, we fabricated biomimic virus-like mesoporous silica coated Ag nanocubes with gentamicin loading, and then the core-shell nanostructure was entrapped in the FDA approved hydrogel dressing. Interestingly, the Ag nanocubes with virus-like mesoporous silica coating are capable of effectively adsorbing on the rigid cell wall of both E. coli and MRSA. The intracellular HS in natural bacterial environment can induce generation of small Ag nanospheres, which are the ideal antibacterial nanoagents. Combined with the gentamicin delivery, the pathogenic bacteria in diabetic wound can be completely eradicated by our dressing to improve the wound healing procedure. This virus-like core-shell nanostructure sheds light for the future wound healing dressing design to promote the clinical applications on antibacterial eradication.
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http://dx.doi.org/10.1016/j.nano.2021.102381DOI Listing
June 2021

Catalytic oxidation of CO on noble metal-based catalysts.

Environ Sci Pollut Res Int 2021 May 24;28(20):24847-24871. Epub 2021 Mar 24.

School of Chemistry and Chemical Engineering, Guizhou University, Guiyang, 550025, Guizhou, China.

Carbon monoxide (CO) catalytic oxidation has gained increasing interest in recent years due to its application prospects. The noble metal catalysts commonly exhibit outstanding CO catalytic oxidation activity. Therefore, this article reviewed the recent research on the application of noble metal catalysts in the catalytic oxidation of CO. The effects of catalyst support, dopant, and physicochemical properties on the catalytic activity for CO oxidation are summarized. The influence of the presence of water vapor and sulfur dioxide in the reaction atmosphere on the catalytic activity in CO oxidation is emphatically discussed. Moreover, this paper discussed several reaction mechanisms of CO catalytic oxidation on noble metal catalysts. Finally, the challenges of removing CO by catalytic oxidation in practical industrial flue gas are proposed.
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http://dx.doi.org/10.1007/s11356-021-13008-3DOI Listing
May 2021

A new frog species of the genus Odorrana (Anura: Ranidae) from Yunnan, China.

Zootaxa 2021 Jan 14;4908(2):zootaxa.4908.2.7. Epub 2021 Jan 14.

Key Laboratory for Conserving Wildlife with Small Populations in Yunnan, Southwest Forestry University, Kunming 650224, Yunnan, China.

The Chinese-Myanmar border area forms part of a long-acknowledged biodiversity hotspot. This region is characterised by dramatic topography and diverse landscapes, which support a high degree of biodiversity and endemism that remains largely understudied. Based on recent survey efforts we here describe a new frog species of the genus Odorrana from this area. Found in Dulongjiang village, Yunnan, China, the new species differs from a morphological perspective from its congeners through the combination of a grass-green dorsum with black posterior spots, absence of dorsolateral folds, a distinct pineal body, presence of supratympanic folds, absence of outer metacarpal, metatarsal and supernumerary tubercles, and a pair of external subgular vocal sacs. From a molecular perspective, pairwise genetic distances of 4.8% to 11.6% for DNA sequences of the mitochondrial gene for 16S ribosomal RNA differentiate the new species from other Odorrana. Our mitochondrial phylogeny suggests that the new species is a deeply divergent genetic lineage clustering with the clade including Odorrana wuchuanensis, and the Odorrana andersonii and Odorrana margaretae groups. The discovery of this new species emphasizes the need for further herpetological studies in the China-Myanmar border region.
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http://dx.doi.org/10.11646/zootaxa.4908.2.7DOI Listing
January 2021

The double-edged roles of ROS in cancer prevention and therapy.

Theranostics 2021 4;11(10):4839-4857. Epub 2021 Mar 4.

Department of Thoracic Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang 110042, China.

Reactive oxygen species (ROS) serve as cell signaling molecules generated in oxidative metabolism and are associated with a number of human diseases. The reprogramming of redox metabolism induces abnormal accumulation of ROS in cancer cells. It has been widely accepted that ROS play opposite roles in tumor growth, metastasis and apoptosis according to their different distributions, concentrations and durations in specific subcellular structures. These double-edged roles in cancer progression include the ROS-dependent malignant transformation and the oxidative stress-induced cell death. In this review, we summarize the notable literatures on ROS generation and scavenging, and discuss the related signal transduction networks and corresponding anticancer therapies. There is no doubt that an improved understanding of the sophisticated mechanism of redox biology is imperative to conquer cancer.
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http://dx.doi.org/10.7150/thno.56747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978298PMC
March 2021

Cytosolic Delivery of Thiolated Neoantigen Nano-Vaccine Combined with Immune Checkpoint Blockade to Boost Anti-Cancer T Cell Immunity.

Adv Sci (Weinh) 2021 Mar 29;8(6):2003504. Epub 2021 Jan 29.

The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University Fuzhou 350025 P. R. China.

Although tumor-specific neoantigen-based cancer vaccines hold tremendous potential, it still faces low cross-presentation associated with severe degradation via endocytosis pathway. Herein, a thiolated nano-vaccine allowing direct cytosolic delivery of neoantigen and Toll like receptor 9 agonist CpG-ODN is developed. This approach is capable of bypassing the endo-/lysosome degradation, increasing uptake and local concentration of neoantigen and CpG-ODN to activate antigen-presenting cells, significantly strengthening the anti-cancer T-cell immunity. In vivo immunization with thiolated nano-vaccine enhanced the lymph organ homing and promoted the antigen presentation on dendritic cells, effectively inhibited tumor growth, and significantly prolonged the survival of H22-bearing mice. Strikingly, further combination of the thiolated nano-vaccine with anti-programmed cell death protein-1 antibody (PD-1) could efficiently reverse immunosuppression and enhance response rate of tumors, which led to enhanced tumor elimination, complete prevention of tumor re-challenge, and long-term survival above 150 d. Collectively, a versatile methodology to design cancer vaccines for strengthening anti-cancer T-cell immunity in solid tumors is presented, which could be further remarkably enhanced by combining with immune checkpoint inhibitors.
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http://dx.doi.org/10.1002/advs.202003504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967047PMC
March 2021

Cytosolic Delivery of Thiolated Mn-cGAMP Nanovaccine to Enhance the Antitumor Immune Responses.

Small 2021 Apr 14;17(17):e2006970. Epub 2021 Mar 14.

MOE Key Laboratory for Analytical Science of Food Safety and Biology, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou, 350116, P. R. China.

As a stimulator of interferon gene (STING), cyclic dinucleotide activates a broad cellular immune response for anti-cancer immunotherapy (CIT). However, the inherent of instability of 2' 3'-cyclic-GMP-AMP (cGAMP) with poor cellular targeting, rapid clearance, and inefficient transport to the cytoplasm seriously hinders cGAMP potency. Here, a thiolated and Mn coordinated cyclic dinucleotide nanovaccine (termed as Mn-cGAMP NVs) to enable direct cytosolic co-delivery of cGAMP and Mn to potentiate the antitumor immune response is presented. In the NVs, the fixation cGAMP with Mn ions not only improve its stability, but also potentiate the activation of STING. Meanwhile, the presence of polysulfides on the NVs surface allowed direct cytosolic delivery while avoiding degradation. In this way, the production of cytokines for activating T cells immunity is greatly elevated, which in turn suppressed the primary and distal tumors growth through long-term immune memory and led to long-term survival of poorly immunogenic B16F10 melanoma mice. Moreover, by further combining with anti-PD-L1 monoclonal antibody, synergistic T cells antitumor immune response is elicited. This work offers a promising strategy to enhance the potency of cGAMP, holding a considerable potential for CIT applications.
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http://dx.doi.org/10.1002/smll.202006970DOI Listing
April 2021

Quantitative Secretome Analysis Reveals Clinical Values of Carbonic Anhydrase II in Hepatocellular Carcinoma.

Genomics Proteomics Bioinformatics 2021 Mar 1. Epub 2021 Mar 1.

Department of Pathology and Institute of Oncology, School of Basic Medical Sciences of Fujian Medical University, Fuzhou 350004, China. Electronic address:

Early detection and intervention are key strategies to reduce mortality, increase long-term survival and improve the therapeutic effects of hepatocellular carcinoma (HCC) patients. Herein, the isobaric tag for relative and absolute quantitation (iTRAQ) quantitative proteomic strategy was used to study the secretome in conditioned medium from HCC cancerous tissues, surrounding noncancerous and distal noncancerous tissues to identify diagnostic and prognostic biomarkers for HCC. In total, 22 and 49 dysregulated secretory proteins were identified in the cancerous and surrounding noncancerous tissues compared with the distal noncancerous tissues. Among these proteins, carbonic anhydrase II (CA2) was identified to be significantly upregulated in the secretome of cancerous tissues; correspondingly, the serum concentrations of CA2 were remarkably increased in HCC patients than that in normal populations. Interestingly, a significant increase of serum CA2 in recurrent HCC patients after radical resection was also confirmed compared with HCC patients without recurrence, and the serum level of CA2 could act as an independent prognostic factor for time to recurrence (TTR) and overall survival (OS). Regarding the mechanism, the secreted CA2 enhances the migration and invasion of HCC cells by activating the epithelial mesenchymal transition (EMT) pathway. Taken together, this study identified a novel biomarker for HCC diagnosis and prognosis and provided a valuable resource of HCC secretome for investigating serological biomarkers.
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http://dx.doi.org/10.1016/j.gpb.2020.09.005DOI Listing
March 2021

Tumor Microenvironment Triggered Cascade-Activation Nanoplatform for Synergistic and Precise Treatment of Hepatocellular Carcinoma.

Adv Healthc Mater 2021 05 28;10(10):e2002036. Epub 2021 Feb 28.

Liver Disease Center, the First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, P. R. China.

Hepatocellular carcinoma (HCC) is one of the most common and deadliest malignancy cancers, which remains a major global health problem. At present, over 50% of patients with HCC have implemented systemic therapies, such as interventional therapy or local chemotherapy that are scarcely effective and induce serious side effects to the remaining normal liver, further limiting their clinical outcomes. Herein, a tumor microenvironment triggered cascade-activation nanoplatform (A-NP ) is prepared based on β-lapachone (β-Lap) and tirapazamine (TPZ) for the synergistic therapy of HCC. The A-NP exerts its targeting effect by binding to the receptor of tumor cells with an external aptamer. In the tumor microenvironment, the nanoplatform can realize H O -triggered disassembly to release β-Lap and TPZ. The released β-Lap generates ROS to induce tumor cell apoptosis under the catalysis of the tumor cell over-expressed NAD(P)H-quinone oxidoreductase-1 (NQO1) enzyme. In this process, oxygen is consumed to intensify tumor hypoxia, and eventually cascade activates TPZ to exert the anti-tumor effect. The studies in vitro and in vivo consistently demonstrate that the as-prepared A-NP nanoplatform possesses an excellent synergistic anti-tumor effect. This design of nanoplatform with cascade activation effect provides a promising strategy for HCC treatment.
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http://dx.doi.org/10.1002/adhm.202002036DOI Listing
May 2021

Diagnostic Value of Neutrophil CD64 in Burn Patients with Infection in Chinese Population:A Systematic Review and Meta-analysis.

J Burn Care Res 2021 Feb 24. Epub 2021 Feb 24.

Department of Burns, People's Hospital of Xinjiang Uygur Autonomous Region,Urumqi city,Xinjiang Uygur Autonomous region,China.

Background: Infection is one of the leading causes of death in burn patients. Many researches regard neutrophil CD64 (nCD64) as a biomarker in the early diagnosis of burn patients with infection. Nevertheless, the conclusions are controversial.

Methods: A comprehensive analysis of the diagnostic value of nCD64 for burn infection was performed in China using a meta-analysis method. Pubmed, Cochrane library, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and China Wanfang databases were searched for studies on nCD64 as a diagnostic biomarker of burn patients with infection from the establishment of the databases to September 29, 2020. The data was analyzed by Stata 15.0 software.

Results: Six studies were identified. The results showed that the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and DOR were 0.92 (95%CI:0.88~0.95), 0.82 (95%CI:0.76~0.87), 5.10 (95%CI:3.90~6.80), 0.10 (95%CI:0.06~0.15) and 52 (95%CI:29~94), respectively. The area under curve (AUC) was 0.94 (95%CI:0.92~0.94). According to the analysis of the sepsis subgroup, it showed that nCD64 had good diagnostic value in the patients with burn sepsis in Chinese population.

Conclusion: nCD64 is highly efficient to diagnose burn infection in Chinese population. Therefore, nCD64 could be regarded as a valuable biomarker for early diagnosis of burn infection in China, especially in patients with burn sepsis. Combined with other diagnostic indexes, nCD64 can be clinically used in the early diagnosis of burn infection to improve the sensitivity and specificity.
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http://dx.doi.org/10.1093/jbcr/irab033DOI Listing
February 2021

Protocol to prepare functional cellular nanovesicles with PD1 and TRAIL to boost antitumor response.

STAR Protoc 2021 Mar 8;2(1):100324. Epub 2021 Feb 8.

The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, P.R. China.

Immunotherapy has achieved notable success in tumor treatment, but it is restricted to a small number of patients due to multiple immunosuppressive pathways in the tumor microenvironment. Here, we present a step-by-step protocol to prepare functional cellular nanovesicles from HEK293-FT cells displaying PD1 and TRAIL. TRAIL specifically induces immunogenic cancer cell death to initiate an immune response, and ectogenic PD1 blocks the PD1/PDL1 checkpoint signal to reactivate anergic tumor-specific CD8+ T cells. For complete details on the use and execution of this protocol, please refer to Wu et al. (2020).
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http://dx.doi.org/10.1016/j.xpro.2021.100324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876612PMC
March 2021

SARS-CoV-2 M inhibitors with antiviral activity in a transgenic mouse model.

Science 2021 03 18;371(6536):1374-1378. Epub 2021 Feb 18.

State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continually poses serious threats to global public health. The main protease (M) of SARS-CoV-2 plays a central role in viral replication. We designed and synthesized 32 new bicycloproline-containing M inhibitors derived from either boceprevir or telaprevir, both of which are approved antivirals. All compounds inhibited SARS-CoV-2 M activity in vitro, with 50% inhibitory concentration values ranging from 7.6 to 748.5 nM. The cocrystal structure of M in complex with MI-23, one of the most potent compounds, revealed its interaction mode. Two compounds (MI-09 and MI-30) showed excellent antiviral activity in cell-based assays. In a transgenic mouse model of SARS-CoV-2 infection, oral or intraperitoneal treatment with MI-09 or MI-30 significantly reduced lung viral loads and lung lesions. Both also displayed good pharmacokinetic properties and safety in rats.
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http://dx.doi.org/10.1126/science.abf1611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099175PMC
March 2021